Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

Quality of life has been used as a primary outcome measure in the treatment of cancer and cardiovascular disease, and as a secondary outcome measure in therapy of Parkinson's disease. However, it has been relatively neglected in studies of amyotrophic lateral sclerosis (ALS). Although there is need for the development of an ALS-specific quality-of-life measure, it will be necessary, nonetheless, to continue to use generic measures in order to ensure comparability of measurement between disease states. An argument is put forward for the use of quality-of-life measures as a primary end-point in future clinical trials in ALS. A distinction is drawn between the demonstration of biological efficacy and clinically useful benefit. The most likely instruments to prove useful are briefly discussed.
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PMID:Health outcome and quality-of-life measurements in amyotrophic lateral sclerosis. 917 68

Methionine metabolism and transmethylation are central to the metabolism and differentiation of all known cells. In enkaryotic organisms, methionine metabolism and transmethylation are of paramount importance in modification and regulation of proteins, lipids, and nucleic acids. The differential methylation of genes regulates their expression in the myriad of cells in eukaryotic organisms. Disruption and abnormalities in methionine metabolism and transmethylation seems to be associated with the major diseases of mankind, including cancer, heart disease, aging, obesity, and Parkinson's disease. In this review, we describe how aberrant and abnormal methionine metabolism and transmethylation are related to these major diseases. Most importantly, we review and hypothesize how the developing therapeutic recombination methioninase (rMETase) can be utilized to cure or prevent all of these diseases.
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PMID:Methioninase: a therapeutic for diseases related to altered methionine metabolism and transmethylation: cancer, heart disease, obesity, aging, and Parkinson's disease. 923 67

Nanomolar concentrations of cytosine arabinoside (ara-C), a structural analogue of 2'-deoxycytidine (2'dC) used in the chemotherapy of cancer, proved to be highly effective in preventing the death of postmitotic dopaminergic neurons that occurs spontaneously by apoptosis in mesencephalic cultures. The rescued cells were totally functional and highly differentiated. The trophic/neuroprotective effects of ara-C were (1) specific for dopaminergic neurons; (2) long-lived, remaining detectable several days after withdrawal of the nucleoside analogue from the culture medium; (3) still observed when the treatment was delayed after plating; (4) abolished by an excess of 2'dC or dCTP, or by exposure to the neurotoxin 1-methyl-4-phenylpyridinium; and (5) mimicked by ara-CTP, 5-fluoro-2'-deoxyuridine, and aphidicolin. Autoradiographic studies revealed that ara-C was incorporated exclusively into astrocyte nuclei, suggesting that the dopaminotrophic activity was indirect and resulted from the antiproliferative action of the modified nucleoside on glial cells at concentrations that were not neurotoxic. No evidence was found for putative deleterious or trophic molecules secreted by proliferating or ara-C-treated astrocytes, respectively, suggesting that neuroglial contact may play a role. Our results suggest a possible mechanism underlying neurodegeneration in Parkinson's disease, where selective loss of dopaminergic neurons in the mesencephalon is accompanied by astrogliosis.
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PMID:Rescue of mesencephalic dopamine neurons by anticancer drug cytosine arabinoside. 932 79

Apoptosis, often synonymously used with the term 'programmed cell death', is an active, genetically controlled process that removes unwanted or damaged cells. Suppression, overexpression or mutation of a number of genes which orchestrate the apoptotic process are associated with disease. The diseases in which apoptosis has been implicated can be grouped into 2 broad groups: those in which there is increased cell survival (i.e. associated with inhibition of apoptosis) and those in which there is excess cell death (where apoptosis is overactive). Diseases in which there is an excessive accumulation of cells include cancer, autoimmune disorders and viral infections. Deprivation of trophic factors is known to induce apoptosis in cells dependent on them for survival. This fact has been exploited in the use of antiandrogens or antiestrogens in the management of prostate or breast cancer. Haemopoietic growth factors like granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin-3 prevent apoptosis in target cells and modulation of levels of these factors has been tried in the prevention of chemotherapy-induced myelosuppression. Until recently, it was thought that cytotoxic drugs killed target cells directly by interfering with some life-maintaining function. However, of late, it has been shown that exposure to several cytotoxic drugs with disparate mechanisms of action induces apoptosis in both malignant and normal cells. Physiological regulation of cell death is essential for the removal of potentially autoreactive lymphocytes during development and the removal of excess cells after the completion of an immune response. Recent work has clearly demonstrated that dysregulation of apoptosis may underlie the pathogenesis of autoimmune diseases by allowing abnormal autoreactive lymphocytes to survive. AIDS and neurodegenerative disorders like Alzheimer's or Parkinson's disease represent the most widely studied group of disorders where an excess of apoptosis has been implicated. Amyotrophic lateral sclerosis, retinitis pigmentosa, epilepsy and alcoholic brain damage are other neurological disorders in which apoptosis has been implicated. Apoptosis has been reported to occur in conditions characterised by ischaemia, e.g. myocardial infarction and stroke. The liver is a site where apoptosis occurs normally. This process has also been implicated in a number of liver disorders including obstructive jaundice. Hepatic damage due to toxins and drugs is also associated with apoptosis in hepatocytes. Apoptosis has also been identified as a key phenomenon in some diseases of the kidney, i.e. polycystic kidney, as well as in disorders of the pancreas like alcohol-induced pancreatitis and diabetes.
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PMID:Apoptosis: clinical relevance and pharmacological manipulation. 933 59

Enormous interest in cell death in the past several years has moved apoptosis to the forefront of scientific research. Apoptosis has been found to mediate cell deletion in tissue homeostasis, embryological development, and immunological functioning. It also occurs in pathological conditions, including cancer and acquired immunodeficiency syndrome, and is implicated in neurodegenerative diseases. Claims of neuronal apoptosis induced by various agents and conditions are published regularly, but in many instances the data are questionable because they are incomplete. This review presents a brief history of apoptosis and describes the evidence required before claims of apoptosis are made. Summaries and critiques of important investigations concerning the genetic and biochemical regulation of neuronal apoptosis are presented, as are other studies describing connections between apoptosis and neuronal cell death in physiological and pathological situations. There is a realization that apoptosis can be programmed and is distinguishable from necrotic cell death. Combining apoptosis with programmed cell death produces misleading terminology and confusion over these two forms of cell degeneration. Further investigations into neuronal apoptosis should focus on all of the criteria that the original investigators outlined 25 years ago, to clarify whether apoptosis and/or another form of cell death mediates neuronal degeneration in physiological settings and in neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, and ischemia/stroke.
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PMID:Apoptosis in neurological disease. 952 91

The use of pesticides has extensively grown in the last decades, regardless of the economic level of the countries. This led to great improvements in agriculture but also a threat for human health. Short term effects are quite well known through approval procedures for pesticides. On the other hand, long term effects are not properly assessed. A review of epidemiologic knowledge is presented here. Epidemiologic studies on pesticides have found associations with long-term effects on health mainly in three fields: cancer (especially hematological cancer), neurotoxic effects (polyneuropathy, neuro-behavioral hazards, Parkinson's disease), and reproductive disorders (infertility, birth defects, adverse pregnancy outcomes, perinatal mortality). These conclusions have been obtained despite difficulties in exposition assessment due to the retrospective nature of the studies. But the continuous development of pesticide use in agriculture, and also in domestic environment, emphasizes the need for epidemiologic studies on long-term effects of pesticides relying on accurate exposure assessment.
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PMID:[Delayed health effects of pesticides: review of current epidemiological knowledge]. 959 56

The human body is exposed to a wide array of xenobiotics in one s lifetime, from food components to environmental toxins to pharmaceuticals, and has developed complex enzymatic mechanisms to detoxify these substances. These mechanisms exhibit significant individual variability, and are affected by environment, lifestyle, and genetic influences. The scientific literature suggests an association between impaired detoxification and certain diseases, including cancer, Parkinson's disease, fibromyalgia, and chronic fatigue/immune dysfunction syndrome. Data regarding these hepatic detoxification enzyme systems and the body s mechanisms of regulating them suggests the ability to efficiently detoxify and remove xenobiotics can affect these and other chronic disease processes. This article reviews the myriad detoxification enzyme systems, their regulatory mechanisms, and the dietary, lifestyle, and genetic factors influencing their activities, as well as laboratory tests available to assess their functioning.
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PMID:The detoxification enzyme systems. 963 Jul 36

Fermented papaya preparation is a natural health food that has been commercially sold in Japan for 2 years. It is made by yeast fermentation of Carica Papaya Linn. We examined the antioxidant action of the fermented papaya preparation on free radicals and lipid peroxidation. Free radicals have been related with aging and diseases, such as cancer, diabetes and especially in neurological disorders, for example, Parkinson's disease or Alzheimer's disease. A diet including variable antioxidant foods may therefore help to prevent these illnesses. The free radical scavenging activity of the fermented papaya preparation was examined using an electron spin resonance (ESR) spectrometer. Fermented papaya preparation (50 mg/ml) scavenged 80% of hydroxyl radicals (.OH) as spin adducts of spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) (5.27 x 10(15)spins/ml) generated by Fenton reagents. The value of IC50 was 12.5 mg/ml. The oral administration of the fermented papaya preparation for 4 weeks decreased the elevated of lipid peroxide levels in the ipsilateral 30 min after injection of iron solution by iron into the left cortex of rats. The fermented papaya preparation also increased superoxide dismutase activity in the cortex and hippocampus of them. These results suggest that the fermented papaya preparation has antioxidant actions and that it may be prophylactic food against the age related and neurological diseases associated with free radicals.
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PMID:Free radical scavenging activity of fermented papaya preparation and its effect on lipid peroxide level and superoxide dismutase activity in iron-induced epileptic foci of rats. 963 26

Toxicologists have thought that the paraoxonase (PON) enzyme polymorphism might contribute to effects of pollutants and other environmental chemicals on susceptibility to cancer, birth defects and Parkinson's disease (PD). We studied a biallelic PON1 polymorphism at codon 192 (A and B alleles) in 166 patients with sporadic idiopathic PD. The frequency of the B (Arg) allele of PON1 was significantly increased in patients with PD than in healthy controls (chi2=8.75, df=1, P<0.005). The relative risk of PD in homozygotes for the B allele was 1.60 fold higher than individuals with the A (Gln) allele (chi2=7.38, df=1, P<0.01). Our data suggest that environmental neurotoxins metabolized by PON1 might be responsible for neurodegeneration with aging and that the B (Arg) allele form might have genetic susceptibility to PD.
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PMID:Genetic polymorphism of paraoxonase 1 (PON1) and susceptibility to Parkinson's disease. 973 48


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